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Chapter 33: Nitrogen: Heme Metabolism

A-18-year-old woman presented with 1-week of history of fever and malaise. She had mild jaundice and elevated temperature. Hemoglobin was 13.8 g/dL, leukocyte count 13 x 109/L. Serum bilirubin was elevated (42 mmol/L) and contained 95% unconjugated bilirubin. Liver enzyme tests were normal. Which of the following is the most likely cause of these signs and symptoms?

A. alcohol poisoning

B. decreased glucuronyl transferase

C. increased lactate dehydrogenase

D. excessive hemolysis

E. obstruction of bile flow

Answer B: Glucuronyl transferase is the enzyme that conjugates bilirubin in the liver, after which it is excreted in bile or urine. A hereditary defect in glucuronyl transferase concentration, or activity, is called Gilbert syndrome. It may lead to mild jaundice and general discomfort with typical onset in childhood or early adulthood. Alcohol poisoning leads to liver damage, and an elevation of conjugated bilirubin. Abnormalities of liver enzyme tests would be expected. Lactate dehydrogenase catalyzes the conversion of lactate to pyruvate as part of cellular energy production. Since many cells including red blood cells are rich in LDH, increased serum LDH levels could point toward excessive hemolysis, but would not be a cause for it. Although hemolysis that exceeds the capacity of the liver to clear bilirubin from serum would lead to increased unconjugated bilirubin, it is not the best choice due to the woman's normal hemoglobin (12-16 g/dL for females). Obstruction of bile flow leads to backup of largely conjugated bilirubin in the blood stream.

An 11-month-old male infant is presented with failure to thrive and a persistence of anemia. Blood analysis revealed levels of lead to be twice the level deemed toxic. Additional laboratory results reveal high levels of coproporphyrinogen III in the urine. In order to rapidly lower the levels of lead in the child's blood, he is placed on chelation therapy. The child recovers fully following this treatment. The symptoms observed in this child are due to the lead-induced inhibition of which of the following enzymes of heme biosynthesis?

A. δ-aminolevulinic acid (ALA) dehydratase

B. δ-aminolevulinic acid (ALA) synthase

C. ferrochelatase

D. porphobilinogen (PBG) deaminase

E. uroporphyrinogen decarboxylase

Answer C: The enzymes ferrochelatase, ALA synthase, and ALA dehydratase are highly sensitive to inhibition by heavy metal poisoning. Indeed, a characteristic of lead poisoning is an increase in ALA in the circulation in the absence of an increase in porphobilinogen. The appearance of coproporphyrinogen III in ...

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